Over the past decade numerous diseases affecting highly active metabolic tissues including the brain and skeletal musculature have been shown to be associated with mutations in the genome of the subcellular organelle, the mitochondria. This organelle is of importance because of its critical role in aerobic metabolism. The genome of this organelle is inherited maternally and a number of diseases have been linked to mutations in this genome. Mendelian, or nuclear, inherited genetic variations and diseases have also been found to affect mitochondrial function, and structure. Previous research in this Laboratory, employing PCR assays to examine brain tissue from 43 age-comparable individuals, demonstrated a correlation between mitochondrial DNA (mtDNA) deletion mutations in specific brain regions and conditions associated with chronic hypoxia. We found 12 fold and 5 fold higher levels of mtDNA deletions in the putamen and the superior frontal gyrus of the cortex respectively. These studies were performed with age matched individuals who had conditions associated with chronic hypoxia when compared with individuals without evidence of such conditions. Further examination of these tissue demonstrated a correlation between a decrease in the levels of genomic DNA adducts, 8-hydroxydeoxyguanine, (8- OHdG), and levels of mtDNA deletions. Previous studies, monitoring translational activity and the efficiency of antibiotic resistance mutations, suggested effects of deletions could not be detected until the deletion levels approached 60% to 10% respectively. However, by measuring 8-OHdG levels in genomic DNA, significant effects could be observed at mtDNA deletion levels as low as 0.01%. In addition, the Laboratory is currently adapting fluorescence in-situ hybridization technologies for use in comparative genomic hybridization to study nuclear and mtDNA genomes in CNS regions in which increased levels of mtDNA deletions have been reported. The Laboratory has established and is maintaining a database on the World Wide Web, Mitodat (http://www-lecb.ncifcrf.gov/mitoDat/). This database contains information on proteins associated with mitochondrial compartments and chromosomal locations of genes encoding mitochondrial associated protein. In addition, the Laboratory has taken the initiative to establish a special interest mitochondria group for the NIH intramural program.